Prostate cancer (PCa) has the second highest incidence of malignancies occurring in men worldwide. The first-line therapy of PCa is androgen deprivation therapy (ADT). Nonetheless, most patients progress to castration-resistant prostate cancer (CRPC) after being treated by ADT. As a second-generation androgen receptor (AR) antagonist, enzalutamide (ENZ) is the current mainstay of new endocrine therapies for CRPC in clinical use. However, almost all patients develop resistance during AR antagonist therapy due to various mechanisms. At present, ENZ resistance (ENZR) has become challenging in the clinical treatment of CRPC. AR splice variant 7 (AR-V7) refers to a ligand-independent and constitutively active variant of the AR and is considered a key driver of ENZR in CRPC. In this review, we summarize the mechanisms and biological behaviors of AR-V7 in ENZR of CRPC to contribute novel insights for CRPC therapy.

Renal cell carcinoma (RCC), as one of the primary urological malignant neoplasms, shows poor survival, and the leading pathological type of RCC is clear cell RCC (ccRCC). Differing from other cell deaths (such as apoptosis, necroptosis, pyroptosis, and autophagy), ferroptosis is characterized by iron-dependence, polyunsaturated fatty acid oxidization, and lipid peroxide accumulation. We analyzed the ferroptosis database (FerrDb V2), Gene Expression Omnibus database, The Cancer Genome Atlas database, and the ArrayExpress database. Nine genes that were differentially expressed and related to prognosis were involved in the ferroptotic prognostic model via the least absolute shrinkage and selection operator Cox regression analysis, which was established in ccRCC patients from the kidney renal clear cell carcinoma (KIRC) cohort in TCGA database, and validated in ccRCC patients from the E-MTAB-1980 cohort in the ArrayExpress database. The signature could be an independent prognostic factor for ccRCC, and high-risk patients showed worse overall survival. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were utilized to investigate the potential mechanisms. The nine genes in ccRCC cells with erastin or RSL3 treatment were validated to find the crucial gene. The glutaminase 2 (GLS2) gene was upregulated during ferroptosis in ccRCC cells, and cells with GLS2 shRNA displayed lower survival, a lower glutathione level, and a high lipid peroxide level, which illustrated that GLS2 might be a ferroptotic suppressor in ccRCC.

Although STK38 (serine-threonine kinase 38) has been proven to play an important role in cancer initiation and progression based on a series of cell and animal experiments, no systemic assessment of STK38 across human cancers is available. We firstly performed a pan-cancer analysis of STK38 in this study. The expression level of STK38 was significantly different between tumor and normal tissues in 15 types of cancers. Meanwhile, a prognosis analysis showed that a distinct relationship existed between STK38 expression and the clinical prognosis of cancer patients. Furthermore, the expression of STK38 was related to the infiltration of immune cells, such as NK cells, memory CD4+ T cells, mast cells and cancer-associated fibroblasts in a few cancers. There were three immune-associated signaling pathways involved in KEGG analysis of STK38. In general, STK38 shows a significant prognostic value in different cancers and is closely associated with cancer immunity.